SIRTMAX Clinical Evidence

Japanese Pharmacology and Therapeutics

Shimada N, et al. Evaluation of the safety and efficacy of Kaempferia parviflora extract (SIRTMAX®) in human: a randomized, double-blind, placebo-controlled crossover clinical study. 2015 Jan;43(7):997-1005.

Topic:
What is the effect of Kaempferia parviflora extract (SIRTMAX) on obesity, glucose and lipid metabolism, and arterial stiffness?

Background:
Kaempferia parviflora is a member of the ginger family. Its rhizome has been reported to inhibit metabolic diseases in mice. Can it have a similar effect on humans?

Study Type:
Human clinical intervention trial

Study Design:
Randomized, double-blind, placebo-controlled. Subjects took 100 mg of SIRTMAX or placebo for 7 weeks. Researchers analyzed blood samples and evaluated arterial stiffness using the cardio-ankle vascular index (CAVI).

Subjects:
27 healthy volunteers

Dosage:
100 mg/day for 7 weeks

Results:
Body weight and fasting blood glucose levels decreased significantly in the treatment group. Weight fell from 74.3+/-1.8 kg to 73.4+/11.8 kg. Fasting blood glucose fell from 106.3+/6.5 mg/dl to 101+/-5.8 mg/dl. For subjects whose HbA1C levels were more than 5.4% (a measure of average blood sugar over the previous 3 months), there was a trend toward improvement in fasting blood glucose and CAVI. Members of the SIRTMAX group also produced fewer advanced glycation end products (AGEs) — which are implicated in diabetes and atherosclerosis — than members of the placebo group. There were no adverse effects during the test.

Conclusion:
“SIRTMAX® had the ameliorative effects on body weight and blood glucose level for all 27 subjects, and improved the vascular function for the subjects with mild hyperglycemia (HbA1c≧5.4%).”

Mechanism of Action:
Kaempferia parviflora is thought to affect metabolism through its effect on adipocytes (fat cells), which are implicated in metabolic diseases. Kaemperferia parviflora may suppress fat accumulation by affecting the differentiation of preadipocytes to adipocytes. Flavonoids contained in Kaempferia parviflora also increase secretion of adiponectin — a hormone that regulates glucose levels and fatty acid breakdown — in in vitro tests. Kaempferia parviflora also activates the SIRT1 pathway, which regulates many aspects of metabolism, including insulin signaling, inflammation modulation, oxidative stress levels, and mitochondrial function. In fact, the whole herb activates SIRT1 five times more than resveratrol, and its flavonoids activate it fifty times more.

Journal of Renal Nutrition

Khajedehi P, et al. Oral supplementation of turmeric decreases proteinuria, hematuria, and systolic blood pressure in patients suffering from relapsing or refractory lupus nephritis: a randomized and placebo-controlled study. 2012 Jan;22(1):50-7.

Topic:
Is turmeric an effective adjuvant therapy for lupus nephritis, an inflammatory disease whose symptoms may include high blood pressure?

Background:
Lupus nephritis is a potentially fatal autoimmune disease, marked by inflammation of the kidneys. Previous research suggests curcumin may decrease the binding of autoantibodies to antigens and may also dial down inflammation.

Study Type:
Human clinical intervention trial

Study Design:
Randomized, placebo-controlled. Subjects took either turmeric or placebo for 3 months. Researchers measured subjects’ urine protein levels (which can indicate damage to the kidneys), urine blood levels, and blood pressure at baseline, and again at 1, 2, and 3 months after intervention.

Subjects:
24 patients with relapsing or refractory lupus nephritis

Dosage:
500 mg turmeric (providing 66.3 mg of curcumin/day)/3x a day for 3 months.

Results:
Turmeric caused significant decreases in protein and blood in the urine as well as systolic blood pressure (the top number, which measures blood pressure between heart beats).

Conclusion:
“Short-term turmeric supplementation can decrease proteinuria, hematuria, and systolic blood pressure in patients suffering from relapsing or refractory lupus nephritis and can be used as an adjuvant safe therapy for such patients.”

Nutrition Journal

DiSilvestro RA, et al. Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people. 2012 Sep 26;11:79.

Topic:
What is the effect of enhanced bioavailability curcumin on a healthy population?

Background:
Curcumin has been linked to various health benefits. However, most studies have been conducted on populations already suffering from existing health problems and use high doses of poorly absorbed curcumin. Can a smaller dose of enhanced bioavailability curcumin contribute to wellness in healthy people?

Study Type:
Human clinical intervention trial

Study Design:
Placebo-controlled

Subjects:
Healthy subjects, aged 40-60 years

Dosage:
80 mg/day of curcumin for 4 weeks

Results:
In the treatment group, the following measurements decreased: triglycerides, salivary amylase levels (high levels of which are associated with several medical conditions), beta amyloid protein (which is implicated in Alzheimer’s disease), sICAM readings (markers of inflammation and immune response), and alanine amino transferase activity (high levels can indicate liver damage, diabetes, or heart disease). Meanwhile, the following measurements increased: salivary radical scavenging capacity, myeloperoxidase (without an increase in c-reative protein—the ratio of these two substances can predict heart disease), and nitric oxide (which can help lower blood pressure).

None of these parameters changed in the placebo group.

Conclusion:
“Collectively, these results demonstrate that a low dose of a curcumin-lipid preparation can produce a variety of potentially health promoting effects in healthy middle aged people.”

Diabetes Care

Chuengsamarn S, et al. Curcumin extract for prevention of type 2 diabetes. 2012 Nov;35(11):2121-7.

Topic:
Can curcumin supplementation delay the development of type 2 diabetes in prediabetics?

Background:
Curcumin has an anti-inflammatory effect. Can it be used to help prevent inflammatory conditions such as diabetes in at-risk populations?

Study Type:
Human clinical intervention trial.

Study Design:
Randomized, double-blind, placebo-controlled. Subjects took curcumin or placebo for nine months. Researchers measured a number of parameters related to the development of diabetes at baseline, 3, 6, and 9 months and tracked how many subjects developed diabetes.

Subjects:
240 subjects with prediabetes

Dosage:
3 250-mg capsules curcumin per day

Results:
At the end of the treatment period, 16.4 percent of subjects in the placebo group had developed diabetes, while no one in the treatment group had. Moreover, the treatment group had better function of beta-cells. The curcumin group also had lower levels of HOMA-IR (a measure of insulin resistance) and higher levels of adiponectin (a protein that regulates glucose) than the placebo group.

Conclusion:
“A 9-month curcumin intervention in a prediabetic population significantly lowered the number of prediabetic individuals who eventually developed T2DM. In addition, the curcumin treatment appeared to improve overall function of β-cells, with very minor adverse effects. Therefore, this study demonstrated that the curcumin intervention in a prediabetic population may be beneficial.”

Indian Journal of Clinical Biochemistry

Maithilli KSN, et al. Efficacy of turmeric as adjuvant therapy in type 2 diabetic patients. 2015 Apr;30(2):180-6.

Topic:
Is curcumin an effective adjuvant treatment for type 2 diabetes?

Background:
Diabetes is characterized by insulin resistance, oxidative stress, high cholesterol, and inflammation. Can curcumin help ameliorate any of these conditions?

Study Type:
Human clinical intervention trial.

Study Design:
Controlled. Subjects took either the diabetes drug metformin alone or metformin plus turmeric for 4 weeks.

Subjects:
60 diabetic subjects taking metformin

Dosage:
2 g turmeric/day for 4 weeks

Results:
· Both groups experienced a significant decrease in fasting glucose levels: the metformin group by 6% and the metformin plus turmeric group by 15%.
HbA1c levels (a measure of average blood sugar over time) also decreased in the metformin plus turmeric group by 5% compared to baseline.
LDL (bad) cholesterol was also lowered in the metformin plus turmeric group compared to the metformin group; the mean percentage of changes between groups was 7.42%.

Conclusion:
“Turmeric supplementation as an adjuvant to T2DM [type 2 diabetes mellitus] on metformin treatment had a beneficial effect on blood glucose, oxidative stress and inflammation.”

The Indian Journal of Medical Research

Deodhar SD, Sethi R, Srimal RC. Preliminary study on antirheumatic activity of curcumin (diferuloyl methane). 1980 Apr; 71:632-4.

Topic:
How does curcumin compare to phenylbutazone (an anti-inflammatory drug) in the treatment of rheumatoid arthritis?

Background:
Curcumin, the active constituent of the Indian spice turmeric, has been traditionally used to treat joint pain. Is it a good alternative to phenylbutazone, a drug with serious side effects?

Study Type:
Human clinical intervention trial.

Study Design:
Double-blind, randomized, controlled trial. Patients with rheumatoid arthritis were treated with curcumin or phenylbutazone.

Dosage:
1,200 mg curcumin per day

Results:
Curcumin improved joint swelling, stiffness, and walking time. Phenylbutazone was even more effective.

Phytotherapy Research

Pungcharoenkul K, Thongnopnua P. Effect of different curcuminoid supplement dosages on total in vivo antioxidant capacity and cholesterol levels of healthy human subjects. 2011 Nov; 25(11):1721-6.

Topic:
How do curcumin and vitamin E compare as antioxidants and in the treatment of elevated cholesterol and triglycerides?

Background:
Heart disease is one of the leading causes of death worldwide, with both free radical damage and high cholesterol considered significant cardiovascular risk factors.

Study Type:
Human clinical intervention trial

Study Design:
Controlled. Subjects took curcumin (at two different doses) or vitamin E. At baseline and after 7 days, researchers measured subjects’ ORAC scores (oxygen radical absorbance capacity, a measure of antioxidant power), cholesterol, and triglycerides.

Subjects:
24 subjects (16 male, 8 female) with a mean age of 29.3 and a mean body mass of 22.7, and all in good health

Dosage:
500 mg/day or 6 mg/day of curcumin or 200 IU/day of vitamin E, for one week.

Results:
In the 500-mg curcumin group, ORAC rose from 13 percent at baseline to 24 percent, while in the higher dose group, ORAC rose only from 19 to 20 percent. Curcumin also caused cholesterol and triglyceride levels to decrease significantly. Vitamin E also raised ORAC scores but it caused only small changes in cholesterol and triglycerides.

Conclusion:
“The dosage of a daily curcumin supplement at 500 mg is more effective than 6 g, although vitamin E is also considered to be an effective antioxidant supplement.”

Surgical Endoscopy

Agarwal KA, et al. Efficacy of turmeric (curcumin) in pain and postoperative fatigue after laparoscopic cholecystectomy: a double-blind, randomized, placebo-controlled study. 2011 Dec;25(12):3805-10.

Topic:
How effective is curcumin at treating pain and fatigue in patients who have undergone a type of gallbladder surgery called laparoscopic cholecystectomy (LC)?

Background:
Turmeric has traditionally been used in India to treat pain and fatigue and for its anti-inflammatory, antioxidant, and healing properties.

Study Type:
Double-blind, randomized, placebo-controlled study

Study Design:
Patents took curcumin or placebo after surgery and kept diaries to record pain, fatigue or other symptoms on a 100-point visual analog pain scale and a 10-point fatigue scale. Researchers followed up with patients after 3 days, 1 week, 2 weeks and 3 weeks.

Subjects:
50 LC patients

Dosage:
500 mg every 6 hours

Results:
Subjects taking curcumin had significantly lower pain scores at 1 week and 2 weeks and significantly lower fatigue scores at 1 week, 2 weeks, and 3 weeks. In fact, after the first week, pain and fatigue scores among those taking curcumin were half that of those taking placebo (15 ± 5.204 versus 30 ± 13). Subjects in the treatment group also took fewer painkillers than those in the control group. After 3 weeks, everyone was pain-free.

Conclusion:
“Turmeric (curcumin) improves postoperative pain- and fatigue-related PROs [patient-reported outcomes] following LC.”

Drugs in R&D

Usharani P et al. Effect of NCB-02, atorvastatin and placebo on endothelial function, oxidative stress and inflammatory markers in patients with type 2 diabetes mellitus: a randomized, parallel group, placebo-controlled, 8-week study. 2008; 9(4):243-50.

Topic:
How does curcumin compare to atorvastatin in the treatment of endothelial function, oxidative stress and inflammation in diabetes patients?

Background:
Elevated blood sugar can cause oxidative stress and poor endothelial function (the endothelium is the interior lining of the blood vessels). Statin drugs can improve this condition, but have side effects. How does curcumin compare to atorvastatin?

Study Type:
Human clinical intervention trial.

Study Design:
Subjects took curcumin, atorvastatin or placebo. Researchers measured endothelial function and collected blood sample to test for malondialdehyde (a marker of oxidative stress), enthothelin-1 (a protein that constricts blood vessels and raises blood pressure), interleukin-6 (a protein involved in inflammation) and tumor necrosis factor-alpha (an inflammatory cytokine).

Subjects:
150 mg/2 times a day, for 8 weeks

Dosage:
72 patients with Type 2 diabetes, 67 completed

Results:
Subjects treated with curcumin or atorvastatin both showed significant improvement in endothelial function compared to placebo and had significant reductions in malondialdehyde, ET-A, IL-6 and TNF-alpha.

Conclusion:
“NCB-02 [a standardized preparation of curcuminoids] had a favourable effect, comparable to that of atorvastatin, on endothelial dysfunction in association with reductions in inflammatory cytokines and markers of oxidative stress.”

Phytotherapy Research

Lal B, et al. Efficacy of curcumin in the management of chronic anterior uveitis. 1999 Jun; 13(4):318-22.

Topic:
Is curcumin an effective treatment for chronic anterior uveitis (an inflammation of the middle layer of the eye)?

Background:
Chronic anterior uveitis, which is sometimes caused by tuberculosis (TB), can be treated with corticosteroids; however they have side effects. Is curcumin a good alternative?

Study Type:
Human clinical intervention study

Study Design:
Subjects without TB took curcumin alone, while those with TB also received anti-tubercular treatment.

Subjects:
53 patients with chronic anterior uveitis, 32 completed

Dosage:
375 mg/3 times a day, for 12 weeks

Results:
All patients receiving curcumin alone improved, while 86% of those also receiving TB treatment did. Follow-up at 3 years showed that there was a recurrence rate of 55% in the curcumin group and 36% in the curcumin plus TB treatment group. The response rate to treatment is similar to that of corticosteroids. There were no reported side effects.

Conclusion:
“The efficacy of curcumin and recurrences following treatment are comparable to corticosteroid therapy which is presently the only available standard treatment for this disease. The lack of side effects with curcumin is its greatest advantage compared with corticosteroids.”

Proprietary Bioavailability Research (Unpublished)

Topic:
How does the bioavailability of MicroActive® Curcumin-SR compare to 95% curcumin powder?

Background:
Curcumin is a promising supplement for inflammation but it is very poorly absorbed.

Study Type:
Human clinical intervention trial

Study Design:
Pilot study. Subjects took MicroActive® Curcumin-SR powder after breakfast. Researchers took blood samples at baseline, 1, 2, 4, 7, and 9 hours. The process was repeated with 95% curcumin powder.

Dosage:
Single dose containing 250 mg curcuminoids

Results:
MicroActive® Curcumin-SR reached maximum blood levels (Tmax) at 2 hours and continued its sustained release until 9 hours. Blood levels remained high at the end of the study period. The 95% curcumin powder took 4 hours to reach Tmax and by 9 hours, levels had dropped to those at baseline, indicating the curcumin took longer to reach the bloodstream and, once there, did not stay active as long.

Conclusion:
“The results indicate the superior bioavailability of MicroActive® Curcumin-SR with a reduction in time to reach maximum blood levels (Tmax) and sustained release for >9 hrs.”

Mechanism of Action:
Curcumin works by countering inflammation and oxidative stress, both of which are implicated in metabolic conditions. Curcumin suppresses pro-inflammatory pathways in multiple ways. It blocks the production of TNF alpha (an inflammatory cytokine), decreases the release of inflammatory interleukins, and inhibits NF-X (an inflammatory protein). It also activates pathways that down-regulate adipokines (fat cell signaling proteins) and up-regulate adiponectin (a hormone that regulates glucose levels and fatty acid breakdown). Finally, it may also affect signal transduction and help regulate the expression of genes involved in free radical scavenging.

MicroActive® Curcumin is more bioavailable than other forms of curcumin, due to its: 1) smaller particle size, which allows it to be incorporated into micelles (a structural unit composed of hydrophilic and hydrophobic parts) and 2) sustained release, due to a special matrix of polymers that keeps the curcumin from precipitating out. Both these factors lead to increased uptake.